On November 15, Arcutis Biotherapeutics announced that its topical phosphodiesterase-4 (PDE4) inhibitor, roflumilast, met its main endpoints in the Phase III INTEGUMENT-1 trial (NCT04773587) for mild to moderate atopic dermatitis (AD) in patients ages six years and older. The treatment of mild to moderate AD is currently managed using a range of topical therapies such as topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), and another established PDE4 inhibitor, Pfizer ’s Eucrisa (crisaborole), which is widely used across the US.
The pivotal Phase III trial of roflumilast 0.15% met its primary endpoint, with 32% of patients who were treated with roflumilast cream 0.15% achieving “IGA success”, defined as a Validated Investigator Global Assessment (IGA) Atopic Dermatitis score of “clear” or “almost clear” plus a two-grade improvement from baseline at week 4. Roflumilast cream also demonstrated rapid improvements compared to vehicle on all secondary endpoints, but most notably in the Eczema Area and Severity Index (EASI )-75, in which 43.2% of subjects saw a 75% reduction in EASI at week 4 compared to 22.0% treated with placebo (P<0.0001). This data is significant because AD is a very prevalent disease, and the mild to moderate group is the most underserved when considering pharmacological disease management. This positive data highlights roflumilast’s utility in this patient population, increasing its potential in such a large disease market.
Safety is becoming a key differentiator among products for AD, and the INTEGUMENT-1 data indicates that roflumilast was well tolerated, with most of the treatment emergent adverse events being mild to moderate. If approved, roflumilast will likely compete with Eucrisa (crisaborole), another topical (PDE4) inhibitor, which is indicated for the treatment of mild to moderate AD in adult and pediatric patients ages three months and older. Eucrisa is a very established product with a strong safety and efficacy profile, as exemplified by its use in patients as young as three months. Thus, a stellar safety profile for roflumilast will be crucial in order for the product to gain market share within the PDE4 inhibitor space, particularly as Eucrisa approaches US patent expiry in 2026.
The prospect of roflumilast entering the AD market is looming as the company is anticipating top line results from a second pivotal trial, INTEGUEMENT-II (NCT04773600), by the end of 2022. In August 2022, the FDA approved Zoryve (roflumilast) for the treatment of plaque psoriasis (PSO ) in patients ages 12 years and older. Arcutis reported strong Q3 sales of $0.7 million for the product, indicating strong uptake due to high patient demand. The company is expected to utilize the commercial infrastructure of the PsO launch to increase exposure in the AD market. GlobalData has projected that roflumilast will enter the US AD market in Q2 2024 and the five major European markets (5EU) (France, Germany, Italy, Spain, and UK) in Q2 2025, reaching total 2030 sales of $80.0 million.